Concerns have been increasingly raised regarding the safety of silicone gel breast implants, with a focus upon whether escaped gel might cause diseases such as progressive systemic sclerosis (scleroderma). The proposed hypotheses to be tested are that: (1) the inflammatory response to silicone is increased in women with silicone breast implants who develop connective tissue disease; and (2) the intensity and duration of this response triggers autoimmune disease in genetically susceptible women. The specific aims are to identify the silicone polymers that are present in tissues from patients with silicone gel breast implants and to characterize their cellular tissue response. The initial approach will be to determine the distribution and quantity of silicone polymers in tissues.This will be accomplished by scanning electron microscopy with X-ray spectroscopy,infrared spectroscopy, gel permeation and gas chromatography and atomic adsorption. Silicone migration studies will be performed to determine the permeability and diffusion of siloxanes of variable molecular weight, using tissue and biomaterial samples obtained from patients with silicone gel breast implants.Similar studies will be performed in mice that have received implants containing silicone. The second approach will be to characterize the cellular and tissue response to silicone polymers. Abnormalities of patients' cellular, humoral and cytokine systems will be investigated by: (1) identification of the cellular composition of involved tissue using histological, immunohistochemical and flow cytometric techniques; (2) evaluation of anti silicone antibody production; and (3) measurement of cytokine transcription and translation. A genetic contribution will be determined by HLA phenotyping. Comparisons will be made among clinically defined groups of patients with breast implants, including those who are asymptomatic, locally symptomatic, and systematically symptomatic with connective tissue diseases. The cellular and tissue response to silicone polymers will also be investigated in mice that have received implants containing silicone.